Echocardiography predictors of clinical outcome in patients with dilated cardiomyopathy.
Abstract: Background

Dilated cardiomyopathy (DCM) is defined as dilatation and impaired contraction of the left or both ventricles and idiopathic DCM is the primary indication for cardiac transplantation. The clinical course is unpredictable. Echocardiography is the definitive tool for diagnosing the presence and type of cardiomyopathy and can provide valuable prognostic information. The most commonly employed technique is the one involving mitral valve inflow patterns and the most important prognostic information is the restrictive filling pattern (RFP).

Patients and Methods

Forty patients with DCM were retrospectively analysed, and clinical and echocardiographic parameters were collected. Adverse events that happened during one year follow-up period were recorded.

Results

Seventeen patients (42.5%) had cardiac events (10 cardiac deaths and 14 rehospitalizations for heart failure). A significant increase of diabetes and S3 gallop among patients with cardiac events was recorded. The left atrial diameter (LAD) at 1-year follow up, the ejection fraction (EF) at baseline and the restrictive filling pattern (RFP) at baseline were associated with positive clinical cardiac events.

Conclusions

According to our results, patients with DCM who had increasing left atrium diameter (LAD) or RFP carried poorer prognosis, so close observation, echocardiographic follow up and intensive medical therapy are needed to avoid cardiac deaths and nonfatal cardiac events. Recent non-medical therapies such as ventricular pacing, implantable cardioverter defibrillator, mitral valve surgery and LV volume reduction could improve the prognosis in patients with DCM if applied in time. For this reason, the echocardiographic predictors are of special value.
Article Type: Report
Subject: Heart failure (Patient outcomes)
Heart failure (Care and treatment)
Heart failure (Complications and side effects)
Cardiomyopathy (Patient outcomes)
Cardiomyopathy (Complications and side effects)
Cardiomyopathy (Care and treatment)
Heart diseases (Patient outcomes)
Heart diseases (Complications and side effects)
Heart diseases (Care and treatment)
Echocardiography (Usage)
Authors: Omar, Ashraf A.
Fouda, Ossama M.
Gad, Yhia Z.
Shahhat, Nader El-
Malky, Nader A. El-
Hakeem, Hazem
Abd El-Samad, Ayman A.
Awad, Mahmoud
Pub Date: 01/01/2010
Publication: Name: International Journal of Health Science Publisher: Renaissance Medical Publishing Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2010 Renaissance Medical Publishing ISSN: 1791-4299
Issue: Date: Jan-March, 2010 Source Volume: 3 Source Issue: 1
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 225792682
Full Text: INTRODUCTION

The aim of this study was to assess echocardiographic and haemodynamic parameters in those patients with DCM and whether these parameters could be predictors to adverse clinical outcome or not, since we can identify patients with poor prognosis and who would benefit from intensive medical therapy or cardiac transplantation.

DCM is defined as dilatation and impaired contraction of the left or both ventricle. (1,2) DCM is responsible for 10,000 deaths and 46,000 hospitalization each year in USA, further idiopathic DCM is the primary indication for cardiac transplantation. (3) DCM can be presented with symptoms of heart failure (exertional dyspnea, or thopnea and paroxysmal nocturnal dyspnea "PND"), arrhythmias, conduction disturbance, thromboembolism or sudden death. Depending on severity and duration patients with DCM can present with New York Heart Association (NYHA) class I to IV symptoms. The clinical course is largely unpredictable in the individual patient and may depend in part upon the cause of the disease. (4) Echocardiography serves as a definitive tool for establishing the presence and type of cardiomyopathy, may provide information regarding specific aetiology and can be used accurately to track the physiologic abnormalities associated with the cardiomyopathy. Additionally, echocardiography and Doppler imaging can provide valuble prognostic information and serves as a guide to success of therapy. (5)

Several echocardiographic and Doppler findings can be related to prognosis in DCM, any of the systolic indices such as ejection fraction can be accurately calculated and are related to prognosis, Doppler ultrasound techniques can also be used to devise prognostic indices. The most commonly employed technique is mitral valve inflow patterns. The Doppler finding carrying the most important prognostic information is the restrictive pattern. This is characterized as a high E/A ratio greater than 2.5 in association with short deceleration time less than 130-150 msec. This pattern indicates a near end stage diastolic dysfunction in which the left ventricle has dilated to the point of reaching mechanical and pericardial constraint. This pattern also implies marked elevation of enddiastolic and left atrial pressures which often seen in patients with more marked degree of left atrial dilation and secondary pulmonary hypertension. (6) Several studies demonstrated that increasing degree of mitral and tricuspid regurgiation correlate with a worsening prognosis. (4)

PATIENTS AND METHODS

Forty patients with documented evidence of DCM were retrospectively analyzed. All baseline clinical characteristics, echocardiographic parameters and other procedural details were collected. Inpatients and outpatients adverse events that happened during the follow up were recorded over one year, such as congestive heart failure (CHF), arrhythmias, conduction defects, thromboembolic complication or sudden death. All patients were subjected after one year follow up to the following:

1- Full clinical exam.

2- Echocardiographic exam with stress on:

a) Dimensions of left ventricle (LVEDD, LVESD, LVM and LVMI).

b) Other cardiac dimensions as (LAD, ARD, IVS).

c) Systolic function (EF and FS).

d) Diastolic function especially IVRT, DT and E/A.

e) Colour Doppler, especially for valvular regurgitation.

f) Pulmonary artery pressure.

Standard long and short-axis and apical two and four-chamber views were obtained with the patient in supine left lateral position in order to measure LV end systolic and end-diastolic diameter indices. The LV ejection fraction (LVEF) was calculated by Simpson's method. (7) Using the pulsed wave Doppler technique from the apical 4 chamber view, the inflow over the mitral valve was obtained, with the sample volume placed at the tips of mitral valve leaflets, E/A ratio and Ewave Deceleration time were calculated from at least 3 consecutive cardiac cycles. A restrictive filling pattern was defined as the presence of E/A ratio > 2 or an E-wave DT < 140 ms. (8)

Statistical Analysis

Normality of distribution of the different variables was assessed by the 1-sample Kolmogorov-Smirnov test. Comparisons of means and medians of continuous data across a factor with 2 levels were done by Student's t-test. Comparisons of proportions were done by the [x.sup.2] test. A 2-sided significance level of 0.05 was used for all analyses, which were conducted using SPSS 15 for Windows (SPSS Inc, Chicago, IL, USA).

Following univariate analysis for each independent variable against the total event outcome, the following were associated with positive event outcome at p [less than or equal to] 0.1 (the entry threshold), and were thus included in the final logistic regression model: DM, smoking, RFP at baseline, DT at baseline, EF at baseline, LVEDD, LAD at 1 year follow-up. This model 4 was also adjusted for the essential confounders (age, gender and body mass index). We found that LAD at 1-year, RFP, and EF at baseline were significantly and independently associated with the positive cardiac events at 1-year follow-up.

RESULTS

Baseline clinical and echocardiographic findings in relation to cardiac events are shown in Table 1. During the follow up period (12 months), there were 17 (42.5%) cardiac events (10 cardiac deaths include 7 patients died due to heart failure and three sudden death, 14 rehospitalizations for heart failure).

Significant increase of diabetes and S3 gallop occured among patients with cardiac events (cardiac deaths, nonfatal cardiac events and total events). Smoking is significantly higher in patients with total events. Patients with cardiac events show higher LVEDD and lower EF than patients without cardiac events. Significant decrease of deceleration time and increase of RFP in patients with cardiac deaths and total events. Table 2 shows changes in echocardiographic parameters in patients with and without cardiac events during the follow-up period. It shows significant decrease of LVEDD and increase of EF in patients without cardiac events and no changes in patients with cardiac events. Significant increase of LAD and RFP in patients with cardiac events and no changes in patients without cardiac events. Table 3 shows multivariate analysis to identify clinical and echocardiographic predictors of adverse clinical events. It reveals that LAD at 1-year follow up, EF at baseline and RFP at baseline are associated with positive clinical cardiac events (cardiac deaths and non fatal cardiac events).

DISCUSSION

Our study confirms relatively poor outcome of patients with DCM. Also it raises the value of various clinical and echocardiographic factors as predictors of cardiac deaths and total cardiac events. In accordance with some studies and in earlier reports the natural history of patients with DCM was of poor prognosis, with mortality rate of 50% at 5 years (9) and despite of advances in medical therapy including angiotensin converting enzyme inhibitors (ACEI) and blockers the prognosis is still relatively poor with a 5 year mortality of 20%. (10)

While in the present study, mortality rate at 1 year follow up was 25% and total cardiac events were 42.5% which is nearly close to study by Kitaoka et al (11) that revealed 9 cardiac events in the 21 patients with mild DCM. In the present study patients with cardiac events showed more left ventricular dilatation and impaired left ventricular systolic function than patients without cardiac events indicating that those patients are more prone to systolic and diastolic wall stress according to Laplace's Law, thus subjecting those patients to more cardiac dilatation, these data are similar to another study which revealed that the degree of LV end diastolic dilation is considered to be one of the primary prognostic predictors in patients with DCM. (12) Patients with cardiac deaths in our study showed significant reduction of both systolic and diastolic functions as evidenced by decrease of EF and DT and increase of RFP, data are similar to results reported by Lapu-Bula et al (13) and a previous report which has elucidated that patients who died of congestive heart failure had a more reduced systolic function. (14) During the follow up period in our study improved systolic function (decrease LVEDD and EF) was observed in patients without cardiac events, despite the absence of clear explanation for that result but possibly because spontaneous improvement in systolic function can occur in patients with DCM. Figulla et al (15) and Steimle et al (16) reported that 27% of patients with recent onset DCM showed improvement of systolic function. Also this may be related to less LV dimensions in those patients. (16) It is also shown during the follow up period that patients with cardiac events had more depressed diastolic function as evidenced by the increase in E/A ratio and RFP, these results are similar to the study of Pinamonti et al. (17)

LAD increased in patients with total cardiac events during the follow up period, this may be due to haemodynamic deterioration because of the higher increase of LV end diastolic pressure in those patients but the precise mechanism remains undetermined. In our study and by multivariate analysis, LAD at 1-year, EF and RFP at baseline are predictors of adverse clinical outcome, this result is supported by Modena et al. (18) who reported that left atrial diameter (> 45 mm) was an independent predictor of prognosis in 123 patients with DCM. Modena et al (18) and Pratali et al (19) who reported that presence of restrictive transmitral flow pattern predicts unfavorable outcome.

CONCLUSIONS

Patients with DCM who had increasing LAD and decreasing EF carried poorer prognosis and presence of RFP is independent predictor of cardiac deaths, so close observation, echocardiographic follow up and intensive medical therapy are needed to avoid cardiac deaths and nonfatal cardiac events. Recent nonmedical therapies such as ventricular pacing, implantable cardioverter defibrillator, mitral valve surgery and LV volume reduction could affect the prognosis in patients with DCM, so further studies with long-term follow-up and large number of patients with DCM are required for evaluation of these recent modalities.

Conflict of interest: None declared.

Corresponding author: Ashraf A. Omar, MD, Faculty of Medicine, Department of Internal Medicine, Mansoura University, Mansoure, Egypt e-mail: ashraf_omar2020@yahoo.com

REFERENCES

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(13.) Lapu-Bula R, Robert A, De Kock M, D'Hondt AM, Detry JM, Melin JA, Vanoverschelde JL. Risk stratification in patients with dilated cardiomyopathy: contribution of Doppler-derived left ventricular filling.Am J Cardiol 1998;82:779-85.

(14.) Romeo F, Pelliccia F, Cianfrocca C, Gallo P, Barilla F, Cristofani R, Reale A.Determinants of end-stage idiopathic dilated cardiomyopathy: a multivariate analysis of 104 patients. Clin Cardiol 1989;12:387-92.

(15.) Figulla HR, Rahlf G, Nieger M, Luig H, Kreuzer H.Spontaneous hemodynamic improvement or stabilization and associated biopsy findings in patients with congestive cardiomyopathy.Circulation 1985;71:1095-104.

(16.) Steimle AE, Stevenson LW, Fonarow GC, Hamilton MA., Moriguchi JD. Prediction of improvement in recent onset cardiomyopathy after referral for heart transplantation. J Am Coll Cardiol 1994; 23: 553-9.

(17.) Pinamonti B, Di Lenarda A, Sinagra G, Camerini F. Heart muscle disease study group: restrictive left ventricular filing pattern in dilated cardiomyopathy assessed by Doppler cardiography: clinical, echocardiographic and hemodynamic correlations and prognostic implication. J Am Coll Cardiol 1993; 22: 808-815.

(18.) Modena MG, Muia N, Sgura FA, Molinari R, Castella A, Rossi R. Left atrial size is the major predictor of cardiac death and overall clinicaloutcome in patient with dilated cardiomyopathy, a long term follow-up study. Clin Cardiol 1997; 20: 553-60.

(19.) Pratali L, Otacervic P, Gherardi S, NeskovicA, Picano E. The additive prognostic value ofrestrictive pattern and dipyridamole-induced contractile reserve in idiopathic dilated cardiomyopathy. Eur J Heart Fail 2005; 7(5):844-51.

Ashraf A. Omar [1], Ossama M.Fouda [1], Yhia Z.Gad [1], Nader El-Shahhat [2], Nader A. El-Malky [1], Hazem Hakeem [1], Ayman A. Abd El-Samad [2], Mahmoud Awad [1]

[1] Department of Internal Medicine and [2] Department of Cardiovascular Disease, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Table 1--Baseline clinical and echocardiographic parameters in
relation to cardiac events

                                      Death

Variables      Yes (n=10)            No (n=30)             p-value

Age            49.3 [+ or -] 7.2     49.1 [+ or -] 6.4     0.923
Male gender    6 (60%)               19 (63.3%)            0.851
BMI            27.9 [+ or -] 5.8     26.5 [+ or -] 4.7     0.437
Hypertension   4 (40%)               4 (13.3%)             0.068
DM             8 (80%)               2 (6.7%)              0.001 *
Smoking        2 (20%)               16 (53.3%)            0.067
HR             78.2 [+ or -] 12      79.5 [+ or -] 8.1     0.692
SBP            114.5 [+ or -] 14.2   107 [+ or -] 11.3     0.097
DBP            73 [+ or -] 4.8       66.8 [+ or -] 8.1     0.032
S3             4 (40%)               0 (0%)                <0.001 *
LAD            27.6 [+ or -] 6.6     30.2 [+ or -] 6.4     0.279
LVEDD          33.9 [+ or -] 5       47.7 [+ or -] 6.6     0.01 *
LVESD          31.3 [+ or -] 4.5     31.2 [+ or -] 4.3     0.983
EF             30.7 [+ or -] 10.6    38.9 [+ or -] 5.7     0.003 *
E/A ratio      1.4 [+ or -] 0.44     1.3 [+ or -] 0.12     0.481
DT             146.1 [+ or -] 14.3   130.4 [+ or -] 18.3   0.018 *
RFP            6 (60%)               2 (6.7%)              <0.001 *

                                 Hospitalization

Variables      Yes (n=14)            No (n=26)             p-value

Age            48.4 [+ or -] 7.7     46.5 [+ or -] 8.1     0.387
Male gender    10 (71.4%)            15 (57.7%)            0.392
BMI            28.1 [+ or -] 6.1     26.1 4.2              0.252
Hypertension   3 (21.4%)             5 (19.2%)             0.868
DM             7 (50%)               3 (11.5%)             0.007 *
Smoking        4 (28.6%)             14 (53.9%)            0.125
HR             80 [+ or -] 4.9       78.7 [+ or -] 9.5     0.687
SBP            112.5 [+ or -] 12.5   106.9 [+ or -] 16.2   0.177
DBP            67.5 [+ or -] 10.9    68.9 [+ or -] 4.9     0.613
S3             2 (14.3%)             2 (7.7%)              0.507
LAD            38 [+ or -] 9.6       30 [+ or -] 6.5       0.531
LVEDD          53.6 [+ or -] 5.3     46.9 [+ or -] 6.3     0.02 *
LVESD          30.5 [+ or -] 4.7     31.7 [+ or -] 4.1     0.411
EF             34.1 [+ or -] 11      38.3 [+ or -] 5.3     0.114
E/A ratio      1.4 [+ or -] 0.37     1.2 [+ or -] 0.12     0.215
DT             137.7 [+ or -] 15.2   132.5 [+ or -] 20.2   0.404
RFP            5 (35.7%)             3 (11.5%)             0.068

                                  Total events

Variables      Yes (n=17)            No (n=23)             p-value

Age            48.8 [+ or -] 3.5     49.7 [+ or -] 8.1     0.64
Male gender    11 (64.7%)            14 (60.9%)            0.804
BMI            28.7 5.8              25.5 [+ or -] 3.9     0.061
Hypertension   5 (29.4%)             3 (13%)               0.201
DM             8 (47%)               2 (8.7%)              0.006 *
Smoking        4 (23.5%)             14 (60.9%)            0.019 *
HR             78.6 [+ or -] 10.2    79.7 [+ or -] 8.4     0.718
SBP            113.2 [+ or -] 12.5   105.7 [+ or -] 11.5   0.544
DBP            69.1 [+ or -] 10.6    67.8 [+ or -] 5.2     0.615
S3             4 (23.5%)             0 (0%)                0.014 *
LAD            28.9 [+ or -] 7.1     30 [+ or -] 5.9       0.593
LVEDD          51 [+ or -] 5.2       52.2 [+ or -] 3.2     0.217
LVESD          39 [+ or -] 4.6       37.9 [+ or -] 4.2     0.678
EF             41.5 [+ or -] 10.2    47.3 [+ or -] 15.1    0.048 *
E/A ratio      1.3 [+ or -] 0.35     1.3 [+ or -] 0.11     0.956
DT             141.7 [+ or -] 16.6   128.9 [+ or -] 18.4   0.031 *
RFP            7 (41.2%)             1 (4.4%)              0.042 *

Table 2--Changes in echocardiographic parameters

               Patients with cardiac events

            Baseline              After 6 month

LAD         28.9 [+ or -] 7.1     30.4 [+ or -] 6.9
LVEDD       51 [+ or -] 5.2       56.1 [+ or -] 3.0
LVESD       39 [+ or -] 4.6       44.4 [+ or -] 3.1
EF          41.5 [+ or -] 10.2    38.5 [+ or -] 11.3
E/A ratio   1.3 [+ or -] 0.35     1.5 [+ or -] 0.49
DT          141.7 [+ or -] 16.6   125.8 [+ or -] 29.5
RFP         7 (41.2%)             8 (47.1%)

               Patients with cardiac events

            After 1 year          p-value

LAD         32.4 [+ or -] 7.9     0.002 *
LVEDD       58.4 [+ or -] 6.0     0.687
LVESD       46.6 [+ or -] 2.5     0.776
EF          36.1 [+ or -] 9.4     0.052
E/A ratio   1.8 [+ or -] 0.44     0.003 *
DT          123.9 [+ or -] 39.2   0.347
RFP         14 (82.4%)            0.032 *

              Patients without cardiac events

            Baseline              After 6 month

LAD         30.0 5.9              30.1 [+ or -] 5.7
LVEDD       52.2 3.2              48.1 [+ or -] 2
LVESD       37.9 4.2              40.6 [+ or -] 5.1
EF          47.3 15.1             49.6 [+ or -] 10.3
E/A ratio   1.3 0.11              1.2 [+ or -] 0.12
DT          128.9 18.4            134.6 [+ or -] 21.7
RFP         1 (4.3%)              2 (8.6%)

              Patients without cardiac events

            After 1 year          p-value

LAD         30.2 [+ or -] 8.6     0.131
LVEDD       46.1 [+ or -] 3.1     0.031 *
LVESD       41.3 [+ or -] 6.1     0.325
EF          62.5 [+ or -] 11.2    0.041 *
E/A ratio   1.2 [+ or -] 0.11     0.141
DT          117.4 [+ or -] 24.9   0.079
RFP         1 (4.3%)              0.812

Table 3--Results of Final Multivariate Logistic Regression Model used
to test the independent association of the input variables with
positive cardiac event outcome

                  [beta]-coefficient   OR      95% CI for OR   p-value

LAD at 1-year     0.168                1.183   1.021-1.369     0.025 *
EF at baseline    - 0.256              0.774   0.652-0.919     0.003 **
RFP at baseline   1.995                7.35    1.287-41.984    0.025 *

Statistical significance at * p<0.05 and ** p<0.001.

OR, odds ratio; CI, confidence interval. Other abbreviations as in
Table 1.
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